DESCRIPTION The long-term objective of this project is to elucidate the mechanisms by which allergen sensitization and viral respiratory illnesses mutually influence one another early in life so as to confer risk for asthma. The relationships of asthma to wheezing lower respiratory illnesses (wLRIs) early in life and to sensitization to certain asthma-related allergens have often been addressed but remain poorly defined. This project proposes and tests a mechanistic basis for these relationships. Three specific aims are proposed: 1) to identify the temporal patterns in and mechanisms of development of mitogen and RSV-specific T cytotoxic cell subsets (CD8+ Tc1 and Tc2) and mitogen and Alt-specific T helper cell subsets (CD4+ Th1 and Th2); 2) to determine the immune mechanisms for the absence of peripheral blood eosinopenic responses during viral respiratory infections in children at risk for asthma; and 3) to identify temporal pattern and the mechanisms of the induction of Alt-specific IgE and RSV-specific IgE in infancy in relation to the occurrence of LRIs and parental history of asthma. A unifying hypothesis is offered that children at risk for asthma may have wLRIs in the third year of life because of a persisting deficiency in cytotoxic function of the CD8+ Tc1 subset of cells, a deficiency which is suggested to originate differently in children with and without a parental history of asthma.